Category Archives: journal

Mark this day as you read this post: you are now officially informed that there are some products certain gifted people who don’t blog are working on, just so that we have a more complicated future in the next decade or two.
For a truly awesome read, try the New Scientist.

Some of the devices that sound as unreal today as Mamata Banerjee’s sanity are as follows:
1. Superman vision: Radar devices the size of briefcases could pass waves through doors and walls and detect the presence of a living man. Think of counter-terrorism.
2. Invisibility Cloaks: we have all read about them in the Wonder Boy’s chronicles. Soon to be a reality, perhaps.
3. Zap-and-stop: A handheld ultrasound device (a high-focus ultrasound) can deliver a zap of sound waves to seal a bleeding vessel. Think US military and DARPA (and the articles I have written on them before).
4. Crouching Tiger Walks: You remember the award-winning Chinese movie where people walk laterally on walls and fly up and down trees as if gravity was only for the rest of us? That could become real in a way, with artificial nano-hairs that can stick to any surface and resist gravitational weights.
5. Jet-log: A backpack on you, and you fly to office. No more pesky office-hour traffic!
6. Translators: personal devices that translate any foreign language while it is being spoken, like they show in that disastrous flick called “From the Subprime to the Ridiculous”, better known as CC2C.
Read that article!

The suggestively titled magazine More has found in a survey that “one in four young women has slept with more than 10 people, compared with one in five men who had done the same”. The poll was held in the UK, as you can read from this article. The new article was mistakenly printed in the New Cars section.

The article does not say how many of these ‘people’ are themselves or their pets, but that will be the contents of another one with 5000 Diggs.

Critics of the survey are quick to point out that while the article says “half of those questioned admitted they had been unfaithful, whereas only a quarter said they had been cheated on by a boyfriend”, it does not specifically say whether the respondents felt they had cheated on themselves by bonking their neighbors’ pets.

The survey also found that most young women would rather sleep with their MacBooks than with the men they married, because they did not believe in sex within marriage and sex with love. For that, they had themselves or their cheat-shits.

Scientists estimate that the average British woman surrenders her virginity as soon as she gets her first iPhone or iPod, which is around infancy, but say that these other events are “mere epiphenomena”. A venerable journal of social science, the SonSun, recently reported that men with condoms stuck on the outside of their shirts were more potent and fertile than men who were more conservative, as deduced from their “wearing underwear over their trousers while catching the Tube.”

A spokesperson for the British Sluttistical Institute claimed that, by the yardstick of the More survey, most people in Britain have had sex with every other. The Secretary of the Institute, Mr. Bansi Lal, stated that the survey needed follow up to prove an exciting new hipothesis that “Indians in UK are the only Indians really getting laid.”

When questioned about the hipothesis being contradicted by the high birth rates in India, Mr. Lal said, “Arrey, that is because we are getting [bleep]ed by those Pakistani [bleep]ers!”

(Indian) Union Health Emperor Mr. Ambumani Ramadoss could not be contacted. His office said he is busy on a mission in the UK.

Ex-Home Minister Shivraj Patil was also unavailable, as he was busy generally [bleep]ing around.

According to certain highly educated and qualified people, Iran could be a surprising model for the rest of the world. No, not just in creating nuclear plants and forcing the West to blink, but in their system of allowing organ trade.
An article in Nature India underpins this point along with some interesting ethics issues. If you do not have access to Nature, you could get the same article here. The author of this piece is a familiar name to some of the readers of this blog, as we have discussed some of his earlier publications.
What is the beef of the article?

In India, a huge demand exists for about 200,000 kidneys, with an estimated annual sale of 2000 kidneys. By making organ sale illegal, this market is pushed underground, and organized rackets thrive by working outside the society’s laws and regulations. One of the spin-offs is the phenomenon of organ theft. Such an organ harvest is obviously illegal. Organ theft and organ sale, however, are not the same thing. Every sane person will surely condemn the stealing of a poor man’s kidney, but if such a person volunteers to sell it for money, would it be all bad?

Ebola is a dreaded name. It is a deadly virus that kills virtually all it infects. It is seen mostly in Africa. The danger of Ebola to the world is because of the real threat of it being used as an agent of bioterror, as I have mentioned in my Foolitzer-winning article on Bioterrorism that appeared in The New York Times an Indian newspaper. In the said article, I reported on the possibility of scientists within terror groups hiding a deadly virus within a benign bacterium which, when treated with antibiotics, would release the virus and cause a highly infectious and lethal disease that could decimate society:

Recently, Popov has talked about an experiment in synthetic biology that fuses plague and Ebola virus. The scientific premise of this Soviet research is to hide a deadly virus particle inside the genome of a more innocuous bacterium.
In this case, infection in the test subject would result in plague like symptoms. Once the treatment (usually tetracycline) for the plague is given, the virus is expressed fully. It is feared that the resultant walking ‘Ebola bombs’ could devastate populations. Ebola, if you didn’t know, has an almost cent percent mortality in man.

Scientists have launched a major attack on the disease by successfully testing a vaccine against Ebola in primates. Human trials are awaited. To read about the challenges of producing an Ebola vaccine, read this interesting and short report.

MIT scientists have invented a sticky tape that will aid healing without the need for stitches. The tape will also break down in time, without needing you to bother about when to go to the surgeon to take it off. These stitches would hold good on the body surface as well as the internal parts.

The adhesive is inspired by geckos’ feet, which allow the reptiles to walk along the ceiling and up and down smooth walls. Gecko toes are sticky because they are covered with millions of flexible nanopillars, giving them a very large surface area. The MIT tape, which relies on both nanoscale pillars and a chemical glue, is the first such tape to show good adhesive strength and safety in animals.

If this tape becomes reality, I predict that entrance exams to go into surgery will finally stop. After all, the most difficult and tricky issues in surgery deal with situations that demand suturing skills of a very high order. Once the need for suturing is gone, all surgeons have to do is to blunder their way into surgery. If they injure anything, they just superglue it. Simple!

Finally, it will prove that surgeons are basically morons with quicker hands, practising what essentially is a monkey science.

In this post, I present a fascinating discussion by some experts on the issues surrounding physicians being involved in judicial execution. This is a topic on which I have been thinking of posting for a while, but I will not offer my views on this now. Just read the transcripts of the interview, which I have taken from the New England Journal of Medicine. If you don’t have the ten minutes needed to read this, I suggest you come back when you do.
A video of the same may be seen here.

THE PROTOCOL

Dr. David Waisel: The three-drug protocol is based on what was considered a normal induction of anesthesia when it was developed. [The first drug is] thiopental, also known as sodium thiopental or pentothal, which is a barbiturate, which is designed to put you to sleep, create amnesia and anesthesia. Second comes pancuronium bromide, which is designed to paralyze the muscles. And the third drug, which is not a drug used in anesthesia, is potassium chloride, which is designed to rapidly stop the heart. The doses used are massive compared to the doses that would be used in a normal anesthetic induction.

Dr. Atul Gawande: You raised, Dr. Truog, [the question of] whether these are the right drugs.

Dr. Robert Truog: We’ve taken a pretty strong stand that paralytic agents have no role in end-of-life care. The concern is that they can mask the behavioral signs that we look to, as to whether or not a patient is comfortable. And we are deeply committed to making sure that patients are comfortable and as free of pain and suffering as possible during the dying process. And since we have medications that do relieve pain, that do sedate perfectly adequately, there’s no need to be introducing paralytic agents into end-of-life care. . . . It’s completely inappropriate to treat those signs and symptoms with a paralytic agent. I think that’s just as true in the execution chamber as in the hospital.

Professor Deborah Denno: According to the state, pancuronium bromide is used in order to enhance the dignity of the inmate who’s dying, because without pancuronium, there might be some jerking or involuntary movements that would disturb some of the witnesses. That I find problematic, and Justice Stevens certainly did.

Dr. Truog: From the point of view of the inmate, the argument seems bizarre. Imagine saying to the inmate, “You have a choice. You can either be assured of a pain-free death, and you may have some twitching and grimacing, or we can expose you to the risk of an excruciating death, but we’ll make sure that you don’t twitch or grimace.” I can’t imagine that an inmate would actually consider that to be a real choice.

ALTERNATIVE APPROACHES

Dr. Truog: The number one alternative that’s been proposed has been a very large dose of a barbiturate. A number of experts have said that 2 or 3 or 5 g of pentothal is absolutely going to be lethal. The fact is that, at least in this country, none of us have any experience with this. And if you look at a country where they do have some experience with it, their findings are pretty concerning.

If we go to Holland, where euthanasia is legal, and look at a study from 2000 of 535 cases of euthanasia, in 69% of those cases, they used a paralytic agent. Now, what do they know that we haven’t figured out yet? I think what they know is that it’s actually very difficult to kill someone with just a big dose of a barbiturate. And, in fact, they report that in 6% of those cases, there were problems with completion. And in I think five of those, the person actually woke up, came back out of coma.

LETHAL INJECTION AND THE EIGHTH AMENDMENT

Dr. Gawande: Professor Denno, [you’ve written that] in turning to this three-drug protocol back in 1977, “The law turned to medicine to rescue the death penalty.” What did you mean by that?

Professor Denno: Lethal injection came about in 1977, a year after the United States Supreme Court decided that there would no longer be a moratorium on the death penalty. And there had been acknowledged problems with electrocution and lethal gas, because of the visual side effects of those methods.

By virtue of coming up with a method of execution that makes an inmate look serene, comfortable, and sleeping during the death process, the death penalty in this country was rescued. The presence of doctors, their involvement, and the association with medicalizing the procedure enhanced its Constitutional acceptability.

Dr. Gawande: What does it mean to be not cruel and not unusual punishment [in compliance with the Eighth Amendment]?

Professor Denno: The Eighth Amendment has never said, nor have the petitioners ever argued, that executions are to be pain-free. The question is whether or not that pain is unnecessary, whether there are alternatives.

Dr. Gawande: Chief Justice Roberts asked, “Do you agree that, if the protocol is properly followed, that there is no risk of pain?”

Dr. Waisel: Define “properly followed.” In other words, the protocols list that this should happen and that should happen. But does that mean if everything happens correctly, if there are no problems with insertion of intravenous catheters, if there’s no problem with mixing up the medications, there’s no problem with delivery of the medications? Then, yes, it would be pain-free.

RISK OF ERRORS

Dr. Truog: I think the issue here is that people go to school for a long time and do years of training in order to be able to do this well. And certainly, everything that I’ve read is that the training for the people that are doing it in lethal injection is nowhere near adequate.

Dr. Gawande: In Kentucky, they have responded to the request by physicians not to have physicians involved. And so it’s staffed entirely by phlebotomists and emergency medical technicians. So how likely is it that errors will occur? By one measure, there have been 40 botched executions out of a little over 900, which suggests a 4-to-5% rate of failure.

Dr. Waisel: We have no idea what the error rate is, because there is no oversight, there is no public reporting. And the information [I] hear worries me. For example, I believe the case was from Missouri, in which they pushed the three drugs, and the inmate didn’t go to sleep. And [they] realized the strap holding the arm was functioning as a tourniquet. So they loosened it up, all the drugs came in at once. Now in that case, I’m highly confident that the inmate experienced a great deal of pain from the potassium chloride. And so I think that your 4-to-5% number is dramatically underestimated.

Dr. Truog: Putting an IV in is not as easy as it may sound. And being certain that it continues to remain in the same place also requires quite a bit of experience, because these catheters can become dislodged, they can go into the tissue, and then they won’t work anymore. Furthermore, we know that many of these inmates, by virtue of their history of drug abuse or obesity or being muscular, can be very difficult to start IVs in.

In a hospital setting, we have a lot of different ways of approaching the situation when we can’t get an IV in. Most commonly, we’ll just put in a central venous line. But that requires a great deal of training. The mixing, the administration of the medications [are] routine in any operating room in this country, but far from routine if you haven’t done it before.

One of the mistakes that I know has occurred happened to me early in my training, when I injected the paralytic agent too quickly after the pentothal, and they precipitated in the tubing. The tubing turned into a piece of concrete. Suddenly, I had no IV. And thank goodness, I was surrounded by very experienced anesthesiologists who stepped in, within moments had another IV. But I know that that has happened in executions, and it could be a disaster.

Dr. Gawande: The petitioners [noted that for] the 3 g of thiopental, no one makes 3 g syringes, so you have to constitute it from small vials of 0.5 g of powder. And several times, whether it’s doctors or non-doctors involved, they’ve simply mixed it up wrong and ended up with much lower doses than they thought.

In Kentucky, the risk of IV infiltration is exacerbated, because they use several feet of tubing, and everybody leaves the room and sits behind a screen where you can’t see the IV sites or monitor how well things are flowing in. And finally, they didn’t have a plan to monitor the depth of anesthesia when you don’t have anybody standing there. And to the extent that there is someone there, they’re not used to being able to assess this.

PHYSICIAN INVOLVEMENT

Dr. Gawande: Now we come to this fundamental question of whether physicians should take charge, to make death less painful. Dr. Truog, what’s your take on [Dr. Waisel’s] question: if you were to be executed, wouldn’t you rather have a capable, specialized physician doing this job?

Dr. Truog: If I think of the kind of a hypothetical where you have an inmate who is about to be executed and knows that this execution may involve excruciating suffering, that inmate requests the involvement of a physician, because he knows that the physician can prevent that suffering from occurring, and if there is a physician who is willing to do that, and we know from surveys that many are, I honestly can’t think of any principle of medical ethics that would say that that is an unethical thing for the physician to do.

Professor Denno: If we’re going to be executing people, I would prefer to have a method of execution where medical expertise would not be necessary. If we’re going to, however, have a method that would be cruel and constitute suffering if we didn’t have doctor involvement, then if there are physicians in the country who are willing to be involved, I would like to think that they would not be chastised or lose their license or be punished by the medical profession for volunteering to take part in an execution, to relieve suffering.

Dr. Truog: There’s been a lot written about whether physicians should participate in torture. And of course physicians shouldn’t participate in torture. But fundamentally, it’s because torture is wrong. And this is [similar] to my views about physician involvement in capital punishment. While I think at one level we can justify it, I think it’s to miss the bigger picture. I really believe that capital punishment is ethically wrong.

Living in the bubble of the United States, it’s easy to lose sight of just how much of an outlier our country is. We stand among a small group of countries that still do capital punishment, [and] I really don’t think we want to be in their company.

REMEDIES

Dr. Gawande: When we come to this question of where can the remedy be found, the directions that seem to be posed are: We involve physicians more and let them treat the prisoner as a patient, or we come up with alternative protocols that don’t involve physicians at all.

Professor Denno: My recommendation has been that there be a panel of experts who would propose a viable method of execution.

Dr. Gawande: It makes me deeply concerned, though, imagining us sitting around a table at a conference, trying to figure out various ways of executing people, and then the prospect of what that becomes, that we figure out that physicians have to be continually actively involved, and we create a specialty of the execution physician.

It may not be possible for the court to say that doctors would be allowed to really treat inmates as patients — control protocol, make judgments about how to make the suffering less or more — and leave them free to have that professional role.

Professor Denno: They’ve been doing that for 30 years. There have been physicians involved in lethal injection since the very first execution in 1982 in this country. Because of secrecy, we’ll never know the full involvement of doctors. But we have many examples of doctors having been involved, who have made these kinds of discretionary judgments about drugs or chemicals and what should be done.

Dr. Gawande: If the court says “We need this to go to an expert panel, with physicians, lawyers, public citizens, to determine a new protocol for execution,” would you participate on that panel? And should other physicians participate on that panel?

Dr. Waisel: It should be wholly permissible for physicians to participate if they wish. I would have to think about it very carefully. A large part would depend on the intellectual freedom involved in the panel, the ability to write a dissenting opinion from what the panel comes up with, and moving away from certain constraints that are put around this that seem not to permit what I would consider to be successful ways of nonphysician involvement.

Dr. Truog: I would not participate on that panel, because I don’t think that capital punishment is ethical. I think other physicians should be free to participate on that panel. And while I wouldn’t want to prejudge how they might come out, I can’t imagine that they are going to be able to develop an evidence base for any other approach that is likely to be successful without the immediate presence of a physician. And then I think we have to grapple with the ethics of that.

The recent controversy about the ENHANCE study is an important illustration of a serious and long-standing problem with the medical profession, and its allied siblings.

What is the ENHANCE study all about? Surely not a penis-enlargement issue, my readers may be forgiven for wondering even fleetingly. Well, it is a study on two treatment modalities for patients with high lipid (cholesterol, for example) levels. But, first, the basics.

You may have high lipid levels because of genetic reasons, or because you eat, drink, or smoke too much. Many of us are obese, too. Traditionally, if you have high cholesterol, apart from the usually discarded ‘lose weight-do exercise’ kind of advice to the patient, your doctor would give you drugs. These lipid-lowering drugs are called, broadly, statins. One of the most common ones today is Lipitor (atorvastatin).

Why is it important to lower cholesterol? Because high cholesterol can lead to fatty plaques being deposited in the coronary arteries (atherosclerosis), leading to a heart attack.

Statins are prescribed to millions of patients around the world, including those with heart disease, hypertension and diabetes (conditions commonly associated with high lipid levels). All statins act by blocking a liver enzyme that normally results in the formation of cholesterol.

The problems with statins are mostly with their cost and side effects. In addition, in a number of patients, they don’t work well enough. Increasing the dose may increase the side effects. So, what can your doctor do in this kind of scenario?

Enter Ezetimibe. This drug reduces the absorption of cholesterol from the intestines, which bear the brunt of all the cholesterol-rich good things in life that the mouth (along with the mind it carries) chases relentlessly.

With me so far?

So, you have statins that reduce cholesterol, and you have ezetimibe, that also does the same in a different way. Why not combine the two? Will surely work better, and reduce the fatty deposits in your coronary arteries, logically. Merck did that in collaboration with Schering-Plough, with Zetia (ezemitibe) and Vytorin (a $5 billion product).
A 30-day course of Vytorin costs around $100, while Zetia costs $93, compared to $32 for a course of generic simvastatin.

That is what the ENHANCE trial was supposed to prove. Unfortunately, it did not show any such benefit.

However, some experts are discounting the trial, saying it is not a fair representation of the truth, that it is botched, and that they would wait for further trials before changing their prescriptions away from Zetia. Around 60% of doctors, however, are likely to stop prescribing the drug. Obviously, it would be a catastrophe for the company, reeling as it still is from the Vioxx losses. Merck stocks have slid down after this trial has come to light.

The important issue that has come up again in this debate is captured in two quotes:

The main problem is that after six years on the market, there are no data for ezetimibe demonstrating any health outcome benefit. In the absence of any demonstrable effect beyond LDL lowering, nearly one million prescriptions per week are written for ezetimibe. Is this rational?

If the ENHANCE trial had shown regression of atherosclerosis or slowed progression, both the company and advocates of ezetimibe would be trumpeting the results as a landmark study. Now that the trial has failed, they describe ENHANCE as a small and unimportant imaging study. You can’t have it both ways!

THAT, ladies and gentlemen, captures a huge truth. Much of what we do as doctors stems from trials that prove one or the other. Products become available commercially, too, and we are tempted or habituated to use them, especially if treated well at cruises and exotic junkets. However, as clinicians, we would still want to do better for the patient, and refine our treatment methods as evidence improves. Therefore, it is vital that we know which data is proven, and which is putative, suggestive or alleged.